Compositions and Methods For Detecting Histamine Related Disorders

Abstract

The present invention generally relates to methods and compositions (e.g., assay kit) for the diagnosis of histamine related disorders. The invention also relates to a novel molecular target of histamine related disorders and the uses thereof for detecting or diagnosing such diseases, as well as to develop adapted and efficient therapeutic treatment thereof. The invention may be used in any mammalian subject, particularly human subjects.

1 - 15 . (canceled) 
     
     
         16 . A method for detecting the presence, stage or type of a histamine related disorder in a subject, the method comprising detecting in vitro or ex vivo the presence of anti-DAO antibodies in a sample from the subject, the presence of such antibodies being indicative of the presence, stage or type of a histamine related disorder in said subject. 
     
     
         17 . The method of  claim 16 , wherein the anti-DAO antibodies are detected by specific ligand binding. 
     
     
         18 . The method of  claim 16 , comprising detecting, in said sample, the presence of anti-DAO antibodies having DAO-inhibiting activity. 
     
     
         19 . The method of  claim 16 , comprising determining in vitro or ex vivo the amount or activity of anti-DAO antibodies in a sample from the subject, comparing such measured amount or activity to a reference or mean value, wherein an increase in such any amount or activity as compared to said reference or mean value is indicative of the presence of such a disease. 
     
     
         20 . The method of  claim 16 , wherein the presence or amount of anti-DAO antibodies is determined using an immunoassay. 
     
     
         21 . The method of  claim 19 , wherein the activity of anti-DAO antibodies is determined by contacting said antibodies with DAO and a DAO substrate, and measuring the presence or amount of transformed substrate. 
     
     
         22 . The method of  claim 16 , wherein the biological sample is selected from tissue samples, biopsies and biological fluids, preferably from total blood, serum, plasma, urine, mucosa, in particular serum, digestive fluid or bronchial fluid, cells substantially purified from mucosal biopsies, such as digestive and respiratory mucosa. 
     
     
         23 . The method of  claim 16 , wherein the histamine related disorder is selected from chronic urticaria, angioedema, asthma, and pseudo allergic reactions, including drug reactions. 
     
     
         24 . A method for detecting the presence or stage of chronic urticaria in a subject, the method comprising detecting in vitro or ex vivo an altered DAO expression or activity in a sample from the subject, such an altered expression or activity being indicative of the presence or stage of chronic urticaria in said subject. 
     
     
         25 . The method of  claim 24 , comprising determining in vitro or ex vivo the level of DAO gene expression in a sample from the subject, comparing such measured level to a reference or mean value, wherein a decrease in such level is indicative of the presence of chronic urticaria. 
     
     
         26 . The method of  claim 24 , comprising determining in vitro or ex vivo the DAO gene polymorphism in a sample from the subject, wherein an increased polymorphism as compared to a reference value or condition is indicative of the presence of chronic urticaria. 
     
     
         27 . The method of  claim 24 , comprising determining in vitro or ex vivo the (relative) amount of DAO protein in a sample from the subject, comparing such measured amount to a reference or mean value, wherein a decrease in such amount is indicative of the presence of chronic urticaria. 
     
     
         28 . The method of  claim 24 , comprising determining in vitro or ex vivo the presence of anti-DAO antibodies in a sample from the subject, such a presence being indicative of the presence of chronic urticaria. 
     
     
         29 . The method of  claim 24 , wherein the biological sample is selected from tissue samples, biopsies and biological fluids, preferably from total blood, serum, plasma, urine, mucosa, in particular serum, digestive fluid or bronchial fluid, cells substantially purified from mucosal biopsies, such as digestive and respiratory mucosa. 
     
     
         30 . A method of assessing the efficacy of a treatment of a histamine related disorder in a subject, the method comprising comparing in vitro or ex vivo the amount or activity of anti-DAO antibodies in a sample from the subject prior to and after said treatment, a decreased amount or activity being indicative of a positive response to treatment. 
     
     
         31 . The method of  claim 30 , wherein the histamine related disorder is selected from chronic urticaria, angioedema, asthma, and pseudo allergic reactions, including drug reactions. 
     
     
         32 . A method of selecting biologically active compounds on histamine related disorders, the method comprising a step of selecting compounds that abolish the presence or reduce the level or activity of anti-DAO antibodies. 
     
     
         33 . The method of  claim 32 , wherein the histamine related disorder is selected from chronic urticaria, angioedema, asthma, and pseudo allergic reactions, including drug reactions.